Orally disintegrating solid pharmaceutical dosage unit containing a partus control substance

Active Publication Date: 2017-10-26
OXYTONE BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a solid dosage unit that is easy to make and suitable for sublingual, buccal, or sublabial administration. Furthermore, the dosage unit does not require storage under temperature control. The method allows for quick and controlled dehydration of an aqueous solution, resulting in a smooth coating and minimal degradation of the active ingredients.

Problems solved by technology

It occurs in more than 10% of all births and is associated with a 1% case fatality rate.
Although active management of the third stage of labour (AMTSL) can prevent up to 60% of PPH cases, PPH continues to have a devastating impact on women in low-resource settings where home births are common and health care facilities are often inaccessible.
Administering the injection, however, requires skill, sterilized equipment, and proper disposal of medical waste.
Oral administration of oxytocin is not a suitable route of administration, since the peptide oxytocin is degraded in the gastrointestinal tract.
In third world countries, it is often practically and / or economically impossible to protect pharmaceutical preparations from the harmful effects of high temperatures and high humidity during transportation, storage and use.
Sublingual administration was considered to be more unpredictable and in addition the pharmacokinetic profile showed an unfavourable latent period.
Also, the sublingual tablets were not stable enough under tropical conditions.
The authors conclude that sublingual administration of oxytocin does not seem a reliable route for immediate prevention of PPH due to ‘long’ lag time and ‘long’ absorption half-life.
The conclusion was that tropical conditions make oxytocin tablets unstable, with humidity as the most adverse factor.
This same need exists for carbetocin and atosiban, especially since currently formulations for in-mouth administration of carbetocin or atosiban are not commercially available.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0121]An oxytocin containing coated powder was prepared by spraying an aqueous solution of oxytocin, citric acid, sodium citrate, zinc chloride, hydrolyzed dextran (Dextran 40) and hydroxypropylmethylcellulose (HPMC) onto mannitol powder in a fluid bed dryer. The spraying solution was prepared by adding the ingredients shown in Table 1 in the amounts indicated to 200 ml of distilled water and adjusting pH to 4.6 (using HCl or NaOH).

TABLE 1IngredientgramsOxytocin0.25Citric acid anhydrate0.27Sodium citrate dehydrate0.80Zinc chloride0.27Dextran 402.5HPMC4.0

[0122]The mannitol powder used had a mass weighted average diameter of 200 μm. The (dry) composition of the dry coated mannitol powder obtained from the fluid bed dryer is shown in Table 2. Estimated water content of the coated powder was 2-3 wt. %.

TABLE 2IngredientWt. %Oxytocin0.16Citric acid0.17Sodium citrate0.51Zinc chloride0.17Dextran 401.58HPMC2.53Mannitol94.88

[0123]Next, the coated powder was combined with excipients (lactose, ...

example 2

[0125]Example 1 is repeated, except that this time more spraying solution is sprayed onto the mannitol powder

[0126]The composition of the dry coated mannitol powder obtained from the fluid bed dryer is shown in Table 4.

TABLE 4IngredientWt. %Oxytocin0.37Citric acid0.39Sodium citrate1.18Zinc chloride0.39Dextran 403.65HPMC5.84Mannitol88.19

[0127]This coated oxytocin powder is combined with excipients (lactose, sodium starch glycolate, ascorbic acid, Ludiflash® and sodium stearyl fumarate) to produce the tablet formulation described in Table 5.

TABLE 5IngredientWt. %Coated powder45.46Lactose10.00Sodium starch glycolate5.00Ascorbic acid2.50Ludiflash ®35.54Sodium stearyl fumarate1.50

[0128]The aforementioned tablet formulation is compressed into tablets of 100 mg. Each tablet contains 0.17 mg (100 I.U.) of oxytocin.

example 3

[0129]Example 1 is repeated, except that this time even more spraying solution is sprayed onto the mannitol powder than in Example 2.

[0130]The composition of the dry coated mannitol powder obtained from the fluid bed dryer is shown in Table 6.

TABLE 6IngredientWt. %Oxytocin0.73Citric acid0.77Sodium citrate2.35Zinc chloride0.79Dextran 407.31HPMC11.69Mannitol76.35

[0131]This coated oxytocin powder is combined with excipients (lactose, sodium starch glycolate, ascorbic acid, Ludiflash® and sodium stearyl fumarate) to produce the tablet formulation described in Table 7.

TABLE 7IngredientWt. %Coated powder45.46Lactose10.00Sodium starch glycolate5.00Ascorbic acid2.50Ludiflash ®35.54Sodium stearyl fumarate1.50

[0132]The aforementioned tablet formulation is compressed into tablets of 100 mg. Each tablet contains 0.33 mg (200 I.U.) of oxytocin.

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Abstract

An orally disintegrating solid pharmaceutical dosage unit having a weight between 50 and 1,000 mg is disclosed. The dosage unit consists of: (a) 5-100 wt. % of coated particles comprising 50-99 wt. % of a core particle and 1-50 wt. % of a coating that envelops the core particle, said coating consisting of:0.01-10 wt. % of a partus control substance selected from oxytocin, carbetocin, atosiban and combinations thereof;5-50 wt. % of buffering agent;15-80 wt. % of branched glucan;0-78 wt. % of other pharmaceutically acceptable ingredients; and(b) 0-95 wt. % of one or more pharmaceutically acceptable excipients;the solid dosage unit comprising at least 20 μg of the partus control substance and having a pH buffer range of 3.5-5.7.

Description

TECHNICAL FIELD OF THE INVENTION[0001]The present invention provides an orally disintegrating solid pharmaceutical dosage unit having a weight between 50 and 1,000 mg, said dosage unit consisting of:[0002]5-100 wt. % of coated particles comprising 50-99 wt. % of a core particle and 1-50 wt. % of a coating that envelops the core particle, said coating consisting of:[0003]0.01-10 wt. % of a partus control substance selected from oxytocin, carbetocin, atosiban and combinations thereof;[0004]5-50 wt. % of buffering agent;[0005]15-80 wt. % of branched glucan;[0006]0-78 wt. % of other pharmaceutically acceptable ingredients;[0007]0-95 wt. % of one or more pharmaceutically acceptable excipients; the solid dosage unit comprising at least 20 μg of the partus control substance and having a pH buffer range of 3.5-5.7.[0008]The solid dosage units of the present invention are particularly suited for sublingual, buccal or sublabial administration of the partus control substance.[0009]The inventio...

Claims

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Application Information

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IPC IPC(8): A61K38/11A61K9/20A61K9/00
CPCA61K38/11A61K9/0056A61K9/2013A61K9/205A61K9/006A61K9/2077A61K9/2018A61K9/2054A61K9/2095A61K9/1652A61K9/1676A61K38/095A61K9/167A61P7/04A61P15/00A61K9/16A61K47/36A61P15/06
Inventor PLATTEEUW, JOHANNES JANCOELINGH BENNINK, HERMAN JAN TIJMEN
Owner OXYTONE BIOSCI
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